tbuckley/cabot-search huggingface dataset:
High-multiplexing quantitative CodePlex proteomic profiling of platelets in triple-negative breast cancer (TNBC) patients and healthy subjects.
Authors: Edward Xu Han, Sean Gu, Matthew Steinle, Vivian Gu, Tarun Tyagi, Sean Mackay, John Hwa, Jing Zhou
Journal: Journal of Clinical Oncology (2022)

e15017 Background: Platelets play significant roles in inflammation, immune regulation, and intracellular communication processes involved in tumor pathogenesis. Aberrant platelet activation has been associated with tumor progression and metastasis, however, cancer patient platelet deep profiling remains underutilized. New tools are needed for rapid high throughput quantification of potential altered platelet secretome in cancer patients. Such technology may provide novel insights into impactful cancer-associated biomarkers. Methods: We have developed a high throughput multiplexed proteomic technology to profile platelet cytokine content and releasates and performed a pilot study in healthy patients versus triple negative breast cancer (TNBC). Macrochambers of the CodePlex chip were pre-patterned with a 23-plex antibody IsoPlexis Human Adaptive Immune Panel: GM-CSF, Granzyme B, IFN-g, IL-10, IL-13, IL-15, IL-17A, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IP-10, MCP-1, MIP-1a, MIP-1b, perforin, sCD137, TGF-b1, TNF-a, TNF-b. 2% BSA/PBS was used as background control. The chips are loaded into an IsoLight automation system, releasates measured by fluorescence ELISA, and analysis performed by IsoSpeak software. In a pilot study to test feasibility, platelets were meticulously harvested from triple negative breast cancer patients (n=2) and healthy controls (n=2) and stimulated for 30 minutes (ADP or TRAP-6) to promote cytokine release. Both the supernatants and platelet lysates were then loaded on CodePlex chips and analyzed. Results: The methodology of bulk proteomic measurements has previously been validated in a variety of biofluids such as serum/plasma, cerebrospinal fluid, tracheal washes, and cell culture supernatants. Freshly isolated platelets activated by TRAP6 generally released more cytokines than those activated by ADP stimulation in both healthy controls and disease samples. Interestingly, platelet releasates in supernatants from TNBC patients demonstrated increased pro-tumor IL-8 and IL-9, and reduced antitumor IFN-g compared to healthy controls. Higher levels of IL-8 and IL-9 and minimal IFN-g were detected at similar activation concentrations, in platelet lysates from both healthy and TNBC platelets. This suggests that TNBC may alter platelet content and/or activation. Increased numbers are being performed to validate these initial results. Conclusions: From this small pilot study, multiplexing quantitative proteomic analysis is potentially useful in detecting differential cytokine profile in platelet releasates and lysate contents between TNBC patients and healthy controls. Quantifying the platelet proteomes in cancer patients using high throughput proteomics may provide valuable insights to dissect cancer-platelet crosstalk and potential pathogenesis mechanisms.
Plenary Session—The Patient Journey: Access to Cancer Care
Authors: Diane K. Hammon, Elizabeth A. Souza, Anne Chiang, Lawrence N. Shulman, Timothy Kubal
Journal: Journal of the National Comprehensive Cancer Network (2022)

As difficult as it may be to comprehend, quality affordable healthcare, particularly cancer care, is not accessible to every individual in every region of the United States. Without timely use of the full range of cancer care services, the best health outcomes cannot be achieved. To explore the scope of this contemporary scenario in cancer care and share ongoing efforts to improve access to cancer care for all, a distinguished panel shared their views at the NCCN 2022 Annual Conference. From the varied perspectives of patients, providers, and researchers, the panel featured a discussion of shared-care models at Massachusetts General Hospital and Penn Medicine Cancer Care to enable patients to expand their access to cancer care and receive that care closer to where they live. In addition, the panel explored initiatives to build and expand the network of clinical trials to enable patients to access such trials in their communities.
A patient perspective on cure in multiple myeloma: A survey of over 1,500 patients.
Authors: Ghulam Rehman Mohyuddin, Jennifer M. Ahlstrom, Cynthia Chmielewski, Nathan W. Sweeney, Thomas H. Molina, Christian S. Cheung, Emily Watabe Ballard, Felicia Seng, Amandeep Godara, Brian McClune, Douglas W. Sborov
Journal: Journal of Clinical Oncology (2022)

8046 Background: As treatments advance in multiple myeloma (MM) and increasingly deeper and longer responses are achieved, the definition of what a cure is becomes increasingly relevant. While many physicians quote that patients may achieve a “functional cure”, understanding the patient perspective on the concept of cure has yet to be explored. Methods: HealthTree Cure Hub by the HealthTree Foundation represents an online portal for patients with plasma cell dyscrasias to help navigate their disease. It is the largest single database of patients with multiple myeloma with over 10,200 patients as of January 2022. Using this platform, we surveyed patients online from November 11 th 2021 to Feb 7 th 2022. Varying scenarios incorporating toxicity, disease status, and being on/off treatment were presented, and participants were asked to rate them from 1-5, with 5 being an ideal cure. Patient awareness of the term functional or operational cure was also. Results: A total of 1525 participants completed the survey. Table lists characteristics of the patients who completed this survey. The majority of the patients were female (55.5%), college educated (88.5%) and non-Hispanic White (70.7%). Most patients rated being off treatment permanently and having no evidence of disease as a cure (1116/1469, 75.5%), with a median score of 5 amongst respondents, indicating an ideal version of cure. Continuing to take the same pill or injection with significant toxicity and no evidence of disease had a median score of 1, a score lower than either “continuing to take same pill or injection without significant toxicity even in the evidence of disease” (median score 2) or “stopping treatment permanently even with some detectable disease” (median score 2). The majority of patients (76.3%) reported being unfamiliar with the term functional or operational cure. Conclusions: In the first study of patients with plasma cell dyscrasias in which patients were asked about their perceptions of what a cure is, our results highlight that drug toxicity and being on treatment profoundly impacts patient's perception of cure. Furthermore, most patients are not familiar with the term functional or operational cure. Future efforts should recruit more diverse patient populations and incorporate patient preferences in approaches to defining cure in myeloma, as well as explaining cure in easily comprehensible terms to patients. [Table: see text]
LGG-56. Surgical management of pre-chiasmatic intraorbital optic nerve gliomas in children after loss of visual function – Resection from bulbus to chiasm
Authors: Julian Zipfel, Jonas Tellermann, Dorothea Besch, Eckart Bertelmann, Martin Ebinger, Pablo-Hernandez Driver, Ulrich-Wilhelm Thomale, Martin U Schuhmann
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION: Optic pathway gliomas (OPG) in children carry significant morbidity and therapeutic challenges. The subgroup of pre-chiasmatic gliomas manifest with exopthalmus are a subgroup where, after blindness has occurred, an intraorbital and intradural resection is a curative option. We present a two-center cohort using two different surgical approaches and describe indication, technique, and long term surgical outcome. METHODS: A retrospective analysis in both centers was performed to included patients &amp;lt; 18 years at diagnosis with a pre-chiasmatic intra-orbital glioma, in whom a resection from the bulb to the chiasm was performed. RESULTS: 11 patients were included. 4 had NF1. Mean age at surgery was 7.0 years. Interval between diagnosis and surgery was 1-74 (median 10) months. Two had prior chemotherapy, one radiation, one both, one prior intraorbital surgery. In all 5 progression occurred. Indications for surgery were exophthalmos, pain, tumor progression or a combination. 8 patients (Group A) underwent an extradural trans-orbital-roof approach to resect intra-orbital tumour including the optic canal part plus intradural pre-chiasmatic resection. In 3 patients (Group B) a combined supra-orbital mini-craniotomy plus orbital frame osteotomy was used for intraorbital tumour-resection, excluding the optic canal part, plus intradural pre-chiasmatic resection. GTR was achieved in 7/8 of Group A and none had a recurrence (mean-FU 42 month). One residual behind the bulbus showed progression, treated by chemotherapy. All residuals in Group B were remnants of the optic nerve within optic canal remained stable (mean FU 11.8 months). No patient had a chiasmatic functional affection or permanent oculomotor deficits. Two after prior radiotherapy developed slight enophthalmos. CONCLUSION: In these selected patients surgical resection from bulb to chiasm (± removal of optic canal tumor) is safe without long-term sequela and with excellent cosmetic result. Surgery removes immediately exophthalmos and provides an effective long-term tumor control. It should be considered therapy of choice.
Five years survival outcomes of head and neck cancer patients treated with palliative metronomic chemotherapy.
Authors: Priyanka Dhanraj Naidu, Vijay Maruti Patil, Vanita Noronha, Kavita Prakash Nawale, Sachin Babanrao Dhumal, Shweta Jogdhankar, Nandini Sharrel Menon, Kumar Prabhash
Journal: Journal of Clinical Oncology (2022)

e18009 Background: Palliative metronomic chemotherapy improved overall survival over intravenous chemotherapy in head and neck cancers. However, there is no data available about the 5-year outcomes with this regimen. Methods: This was a single-arm prospective study that enrolled head and neck squamous cell carcinoma patients warranting palliative chemotherapy. The chemotherapy administered was methotrexate 15 mg/m2 per oral weekly and celecoxib 200 mg per oral daily till the development of intolerable side effects or progression. Kaplan Meier method was used for estimation of OS and factors impacting the same were sought. A p-value of 0.05 was considered significant. Results: 200 patients were enrolled with a median age was 49.5 years (Range 22-85 years) and preponderance of male gender (175, 87.5%). The predominant site of malignancy was oral cavity in 144 patients (72.2%). Prior chemotherapy exposure was present in 78 patients (39%). The median FACT trial outcome index score was 43.7 (16.7-80.7). The median OS was 194 days (95%CI 181.7-206.3) . The 1-year, 3-years and 5-years OS were 17 %(Standard error-2.8%), 7.9% (Standard error-2.5%), and 3.9% (Standard error- 2%) respectively. The details of factors impacting OS are given in Table. Conclusions: Oral metronomic chemotherapy leads to a small proportion of patients having long term survival with metronomic chemotherapy. Clinical trial information: CTRI/2015/11/006392. [Table: see text]
The effect of race, employment, and poverty on outcomes in chimeric antigen receptor therapy for DLBCL patients.
Authors: Grace Johnson, Kedar Patel, Michael D. Jain, Brandon Jamaal Blue
Journal: Journal of Clinical Oncology (2022)

e18506 Background: Limited information is known about how socioeconomic (SES) factors contribute to outcomes after CAR T-cell therapy for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). While racial and SES disparities have been demonstrated to effect outcomes after Autologous Stem Cell Transplant for DLBCL patients, little is known about this association after CAR T. Methods: Using data from Moffitt Cancer Center's electronic medical record system, we retrospectively evaluated patients diagnosed with DLBCL at our center who underwent CART therapy (n = 200). Data was analyzed by residential area deprivation index (ADI) for patients receiving CAR T therapy for R/R DLBCL at a single tertiary care center. Survival and CAR T-related toxicity outcomes were evaluated based on patient baseline characteristics, disease features, and demographics using multivariable Cox proportional-hazards (PH) regression model and multivariable logistic regression model. Patient socioeconomic status was represented by area deprivation index ranking mapped through 9-digit zip codes. Results: The study included 200 patients receiving CAR T therapy at Moffitt Cancer Center for R/R DLBCL; median age was 65; 46.8% were female, 53.2% male; 89.8% white, 10.2% non-white; median ADI rank of 4. As for disease characteristics; 18.9% had double/triple hit lymphoma by FISH for MYC and BCL2 or 6 translocations; 83.6% had extranodal disease sites. Patients were treated with a median of 3 prior lines of therapy, and most patients (81%) had stage III/IV lymphoma at time of leukapheresis for CAR T. 8.38% of patients experienced grade 3 or higher cytokine-release syndrome (CRS), and 34.6% of patients experienced grade 3 or higher neurotoxicity. Area deprivation index and education level did not significantly contribute to overall survival when adjusted for other clinical features on multivariable Cox PH regression analysis. However, unemployment negatively impacted overall survival (HR = 4.296, P = 0.0243). Progression-free survival was unaffected by ADI, education level, or employment. In terms of CAR T-related toxicities, demographic features did not affect the risk for grade 3 CRS on multivariable logistic regression model. On Wilcoxon rank testing, area of deprivation indices did not significantly differ among patients with or without grade 3 CRS. Conclusions: These results suggest that ADI and other SES factors do not significantly contribute to progression free survival, CRS or neurotoxicity. This study shows unemployment was a significant predictor for poor overall survival after CAR T in patients with DLBCL. This is the first study to evaluate the significance of SES, race, and employment on DLBCL patients after CAR T. Future efforts should be used to investigate measures to increase employment and understand factors associated with unemployment.
The C-type Natriuretic Peptide: a new player in the development of the Marfan syndrome?
Authors: S Clerc, C Bielmann, K Bouzourene, T Deglise, L Mazzolai, N Rosenblatt-Velin
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): CHUV Background Marfan Syndrome (MFS) is an autosomal dominant inherited connective tissue disorder affecting the cardio-vascular system. Aortic dissections and ruptures are the primary cause of morbidity and mortality in these patients. MFS is a genetic disorder due to mutations in the Fibrillin1 gene or in genes coding for the proteins of the TGF-beta signaling pathway. No treatment really cures Marfan patients. Interestingly, in humans, mutations in the gene coding for the C-type natriuretic peptide (CNP) or its receptors lead to a "Marfan-like syndrome". CNP is a local regulator of skeletal growth and of vascular homeostasis, remodeling and angiogenesis. CNP binds to two receptors, NPR-B and NPR-C, expressed on endothelial and smooth muscle cells (SMCs). CNP is constitutively released by endothelial cells, whereas TGF-beta stimulates its secretion by SMCs. The aim of this project is to determine whether altered CNP signaling pathway contributes to the development and progression of the vascular dysfunctions in MFS. Methods Plasma and vessel biopsies were taken from Marfan patients (RAVAD registery, CHUV Lausanne) and from Fbn1C1041G/+ mice, a mouse model which recapitulates several of the human phenotypes, including aortic wall degeneration and aneurysm development. CNP and TGF-beta concentrations were measured in the plasma. CNP, NPR-B and NPR-C protein levels were evaluated by Western blot analysis in aortic tissue during the development of MFS. In parallel, human and mouse SMCs were isolated and cultured in vitro with different CNP concentrations. Results CNP plasma concentration was decreased in Marfan patients compared to age and sex-matched non-Marfan patients (18 pmol/l versus 310; p=0.07). Two fold less CNP protein level was detected in the abdominal aorta of a Marfan patient. In 6-7 week-old male Fbn1C1041G/+ mice, CNP protein levels were 1.5 and 2.5-fold increased in the ascending and descending aorta, respectively. NPR-B and NPR-C protein levels remained unchanged. In 24 week-old Marfan male mice, CNP protein level was normalized. In female mice, we detected no alterations of the CNP protein level but the NPR-B and NPR-C protein levels were decreased in the descending aorta 6 and 24 weeks after birth, respectively. In vitro, CNP simulates both human and mouse SMC proliferation in a dose-dependent manner (+ 40% for human SMCs stimulated with 0.02 nM CNP). Conclusion Our results suggest that the early step of the syndrome is associated with high level of CNP (detected in 6 week-old male mice), whereas the late advanced stage of the disease is associated with decreased CNP protein level (detected in Marfan patients). These results could open the door to new therapies for Marfan patients.
Pivotal study of ofra-vec (VB-111) combined with paclitaxel versus paclitaxel for treatment of platinum-resistant ovarian cancer (OVAL, VB-111-701/GOG-3018).
Authors: Richard T. Penson, Rebecca Christian Arend, Angeles Alvarez Secord, Antonio Casado Herraez, Thomas J. Herzog, Jonathan A. Ledermann, Kathleen N. Moore, Ronnie Shapira-Frommer, Krishnansu Sujata Tewari, Tamar Rachmilewitz Minei, Dror Harats, Shifra Fain Shmueli, Bradley J. Monk
Journal: Journal of Clinical Oncology (2022)

TPS5606 Background: Ofranergene obadenovec (Ofra-vec, VB-111) is an anti-cancer gene based immune activator and targeted vascular disruptor. The dual mechanism of action triggers a broad antiangiogenic effect and induces of a tumor directed immune response. A phase II trial in patients with platinum resistant ovarian cancer (PROC) demonstrated that ofra-vec in combination with weekly paclitaxel was well tolerated and associated with a CA-125 Objective Response Rate (ORR) of 58%, a trend for improved survival and induction of an immunotherapeutic effect of tumor infiltration with CD-8 T cells. Based on these observations, a pivotal phase III study was initiated in collaboration with the GOG Foundation, Inc. Methods: Study NCT03398655 is an international, randomized, double-blind, placebo-controlled, phase III study. Eligible patients have recurrent PROC and may have been previously treated with up to 5 prior lines of therapy (but not &gt;2 for PROC). Patient are randomized 1:1 to receive ofra-vec (1x10 13 Viral Particles) with weekly paclitaxel (80mg/m 2 ), or weekly paclitaxel with placebo. Randomization is stratified by number of prior treatment lines, prior antiangiogenic therapy and platinum refractory disease status. The dual primary endpoints are OS and PFS. A pre-planned interim analysis of CA-125 response (GCIG) performed by the DSMC met the pre-defined criteria showing that CA-125 ORR in the treatment arm was at least 10% higher than in the control arm. Study is enrolling in the US, EU, Japan and Israel, with 90% enrollment to date. Completion of accrual is anticipated in Q1 2022. Clinical trial information: NCT03398655.
3D modeling of renal tumors for planning and guidance of selective clamping and urinary collecting system suture
Authors: R. Schiavina, L. Bianchi, L. Cercenelli, B. Bortolani, P. Piazza, S. Boschi, M. Droghetti, A. Mottaran, F. Chessa, A. Ercolino, A. Angiolini, S. Lodi, A. Pissavini, L. Fontanella, L. Spinozzi, R. Melloni, F. Bevilacqua, D. Cangemi, C. Gaudiano, B. Corcioni, R. Golfieri, E. Marcelli, E. Brunocilla
Journal: European Urology (2022)
Is there an added value of dynamic MRI of the pelvic floor to the Clinical POP-Q Examination before management of Pelvic Organ Prolapse in females? A double blinded prospective study in a tertiary care center
Authors: A.F. Hussein, R.F. Elsayed, N. Mahfouz, A.Y. Abdelaziz, M.S. Aldelazim, H.A. Hussein
Journal: European Urology (2022)
Relationship between tumor infiltrating lymphocytes and clinicopathological features in Peruvian gastric cancer.
Authors: Carlos Arturo Castaneda Altamirano, Miluska Castillo Garcia, Luis A. Bernabe, Joselyn Sanchez, Matteo Fassan, Katherine Tello, Iván Chávez, Eloy Ruiz, Fernando Barreda, Daniel Valdivia, Yaqueline Bazan, Milagros Abad, Ebert Poquioma, Paola Catherine Montenegro, Luis Taxa
Journal: Journal of Clinical Oncology (2022)

e16080 Background: Role of tumor-infiltrating lymphocytes (TIL) over clinicopathological features including Mismatch Repair (MMR), HER2 status, Epstein Barr Virus (EBV) and Helicobacter pylori (HP) infection is not well understood in gastric cancer (GC). Methods: TIL level and HP infection was also evaluated in H&amp;E from 503 Peruvian GC patients who underwent surgery. Density of CD3+ T cells, CD8+ cytotoxic T cells, CD163 M2 macrophages, as well as MMR and HER2 status were determined by immunohistochemistry. HP and EBV infection was also detected by qPCR in a 234 cases subset. Results: Median age was 62 years and 50.1% were female, most tumors were grade 3 (59.1%), intestinal subtype (44.8%) and stage III (59.8%). MMR loss was found in 29.4% and HER2+ in 4.7%. HP+ was detected by H&amp;E in 55.7% and by qPCR in 63.7%. EBV+ by qPCR was found in 20.5% and co-infection along with HP in 9.4% (22/234). Stage (p &lt; 0.001), intestinal histology (IH) (p = 0.019), grade (p = 0.006) and lymphovascular invasion (p &lt; 0.001) were associated with longer survival. Median TIL was higher in invasive border (IB) and stromal (ST) than intratumoral (IT) compartment but there were significantly correlated (p &lt; 0.001). High IT TIL was associated with absence of HP H&amp;E (p = 0.009). High ST TIL was associated with older age (p &lt; 0.001), IH (p &lt; 0.001), grade 1 (p = 0.009), lower stage (p = 002), MMR loss (p = 0.019) and EBV+ (p = 0.001). Density of CD3 and CD8 were significantly correlated in IT and ST compartments (p &lt; 0.001). High CD3 density in IT compartment was associated with grade 3 (p = 0.001) and HP- (p = 0.02), and in ST was associated with IH (p = 0.005), grade 1- 2 (p = 0.002) and MMR loss (p = 0.04). High IT CD8 was associated with HER2- (p = 0.016), HP- (p = 0.014) and EBV+ (p = 0.012). High ST CD8/CD3 ratio was associated with diffuse histology (p = 0.034), grade 3 (p = 0.013), more advanced stage (p = 0.022) and recurrence (p = 0.014). High ratio of IT CD8/CD3 was associated with MMR loss (p = 0.007). High ST TIL was associated with longer DFS (p = 0.007). Lower ratio of CD8/CD3 was associated with longer OS (p = 0.024) and DFS (p = 0.02). Conclusions: TIL levels and infiltrating immune subpopulations differs by clinicopathological features in GC including MMR loss, HER2 expression EBV and HP infection. ST CD8/CD3 was associated with recurrence and shorter DFS.